A Study of Trastuzumab Emtansine in Comparison With Treat... | NCT01419197

ID	Type	Description	Link
BO25734	Other Identifier	Hoffmann-La Roche
2011-000509-29	EudraCT Number

Label	Type	Description	Intervention Names
Trastuzumab emtansine	Experimental	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Drug: Trastuzumab emtansine
Treatment of physician's choice	Active Comparator	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.	Drug: Treatment of physician's choice

Name	Type	Description	Arm Group Labels	Other Names
Trastuzumab emtansine	Drug	The dose was calculated based on the patient's Baseline weight on Day 1 of each 3-week treatment cycle. The same dose was administered in subsequent cycles if the patient's weight stayed within 10% of the Baseline weight. If there was a weight change > 10%, the dose was adjusted accordingly and the recorded weight became the new Baseline weight. Trastuzumab emtansine was provided as a single-use lyophilized formulation.

Measure	Description	Time Frame
Progression-free Survival	Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Overall Survival	Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Measure	Description	Time Frame
Percentage of Participants With an Objective Response	An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

PubMed Identifier	Type	Citation	Retractions
28733983	Derived	Chen SC, Quartino A, Polhamus D, Riggs M, French J, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Jin JY, Girish S, Li C. Population pharmacokinetics and exposure-response of trastuzumab emtansine in advanced breast cancer previously treated with >/=2 HER2-targeted regimens. Br J Clin Pharmacol. 2017 Dec;83(12):2767-2777. doi: 10.1111/bcp.13381. Epub 2017 Sep 3.
28526538

ID	Title	Description
FG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
FG001	Treatment of Physician's Choice

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival

Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.

Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Units	Counts
Participants	OG000404 OG001198

Title

Denominators

Categories

Title	Measurements
	OG0006.2(5.59 to 6.87) OG0013.3(2.89 to 4.14)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or > 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).	Log Rank		<0.0001	The two-sided stratified log-rank test was used to compare progression-free survival between the two treatment arms at the overall two-sided significance level of 0.5%.	Hazard Ratio (HR)	0.528			2-Sided	95	0.422	0.661			The hazard ratio was estimated by Cox regression.	No

Primary

Overall Survival

Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.

Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Units	Counts
Participants

Secondary

Percentage of Participants With an Objective Response

An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.

Randomized population: All participants who were randomized to the study. Only participants with measurable disease at Baseline were included in the analysis. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Secondary

Duration of the Objective Response

Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.

Randomized population: All participants who were randomized to the study. Only participants with an objective response were included in the analysis. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Secondary

6-month and 1-year Survival

6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.

Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Units	Counts
Participants

Secondary

Time to Pain Symptom Progression

Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain.

Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice

Secondary

Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle

The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Secondary

Overall Survival (Final Analysis)

Overall survival was defined as the time from randomization to death from any cause.

Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Units	Counts
Participants

Secondary

6-month and 1-year Survival (Final Analysis)

6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.

Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

ID	Title	Description
OG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
OG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0012 affected184 at risk EG0021 affected94 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0017 affected184 at risk EG0020 affected94 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0012 affected184 at risk EG0020 affected94 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Cardiac failure	Cardiac disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hypercalcaemia of malignancy	Endocrine disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Vision blurred	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected403 at risk EG0013 affected184 at risk EG0021 affected94 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Abdominal wall haematoma	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Colitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Ileus	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0012 affected184 at risk EG0020 affected94 at risk
Obstruction gastric	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Proctitis Haemorrhagic	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0021 affected94 at risk
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0012 affected184 at risk EG0020 affected94 at risk
Adverse drug reaction	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Asthenia	General disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Death	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Device occlusion	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Fatigue	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
General physical health deterioration	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Malaise	General disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Non-cardiac chest pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Oedema peripheral	General disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0012 affected184 at risk EG0020 affected94 at risk
Pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Pyrexia	General disorders	MedDRA (16.0)	Systematic Assessment	EG0007 affected403 at risk EG0012 affected184 at risk EG0021 affected94 at risk
Vessel puncture site haemorrhage	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Nodular regenerative hyperplasia	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Hypersensitivity	Immune system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Appendicitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Bronchopneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Cellulitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0014 affected184 at risk EG0021 affected94 at risk
Clostridium bacteraemia	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Device related infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Device related sepsis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Gastroenteritis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Infected fistula	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Infectious colitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Lung infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Lymphangitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Mastitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Neutropenic sepsis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Pneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0005 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Postoperative wound infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Sepsis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0003 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Sinusitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Tracheitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0004 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Urosepsis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Wound infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Sternal fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Traumatic intracranial haemorrhage	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Wound decomposition	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Wound haemorrhage	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Transaminases increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
White blood cell count decreased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Ataxia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Brain oedema	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Cerebral haematoma	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Cognitive disorder	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Dizziness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Loss of consciousness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Paraesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Paraparesis	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Seizure	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Somnolence	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Visual field defect	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Confusional state	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Haematuria	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0006 affected403 at risk EG0015 affected184 at risk EG0022 affected94 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Non-cardiogenic pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Obliterative bronchiolitis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected403 at risk EG0012 affected184 at risk EG0020 affected94 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0012 affected184 at risk EG0021 affected94 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0002 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Embolism	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Embolism venous	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0020 affected94 at risk
Hypertensive crisis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hypotension	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Lymphoedema	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0011 affected184 at risk EG0021 affected94 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Abdominal infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Biliary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Epilepsy	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Hemiplegia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk
Pulmonary Fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0021 affected94 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00045 affected403 at risk EG00119 affected184 at risk EG0027 affected94 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0009 affected403 at risk EG00111 affected184 at risk EG0020 affected94 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00030 affected403 at risk EG00139 affected184 at risk EG0025 affected94 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00081 affected403 at risk EG0016 affected184 at risk EG00217 affected94 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00027 affected403 at risk EG00120 affected184 at risk EG0029 affected94 at risk
Constipation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00090 affected403 at risk EG00132 affected184 at risk EG0027 affected94 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00052 affected403 at risk EG00140 affected184 at risk EG00210 affected94 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00051 affected403 at risk EG0012 affected184 at risk EG0029 affected94 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00021 affected403 at risk EG00112 affected184 at risk EG0020 affected94 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00021 affected403 at risk EG0010 affected184 at risk EG0020 affected94 at risk
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG000144 affected403 at risk EG00140 affected184 at risk EG00216 affected94 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00013 affected403 at risk EG00111 affected184 at risk EG0020 affected94 at risk
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00077 affected403 at risk EG00116 affected184 at risk EG00210 affected94 at risk
Asthenia	General disorders	MedDRA (16.0)	Systematic Assessment	EG00076 affected403 at risk EG00133 affected184 at risk EG00215 affected94 at risk
Chills	General disorders	MedDRA (16.0)	Systematic Assessment	EG00021 affected403 at risk EG0014 affected184 at risk EG0020 affected94 at risk
Fatigue	General disorders	MedDRA (16.0)	Systematic Assessment	EG000123 affected403 at risk EG00148 affected184 at risk EG00210 affected94 at risk
Influenza like illness	General disorders	MedDRA (16.0)	Systematic Assessment	EG00021 affected403 at risk EG0012 affected184 at risk EG0020 affected94 at risk
Mucosal inflammation	General disorders	MedDRA (16.0)	Systematic Assessment	EG00017 affected403 at risk EG00110 affected184 at risk EG0027 affected94 at risk
Oedema peripheral	General disorders	MedDRA (16.0)	Systematic Assessment	EG00026 affected403 at risk EG00111 affected184 at risk EG0020 affected94 at risk
Pyrexia	General disorders	MedDRA (16.0)	Systematic Assessment	EG00077 affected403 at risk EG00122 affected184 at risk EG00214 affected94 at risk
Nasopharyngitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG00035 affected403 at risk EG00112 affected184 at risk EG0026 affected94 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG00035 affected403 at risk EG0018 affected184 at risk EG0028 affected94 at risk
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG00026 affected403 at risk EG0017 affected184 at risk EG0029 affected94 at risk
Alanine aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG00038 affected403 at risk EG00110 affected184 at risk EG0027 affected94 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG00051 affected403 at risk EG00113 affected184 at risk EG00213 affected94 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG00021 affected403 at risk EG0015 affected184 at risk EG0027 affected94 at risk
Blood bilirubin increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG00038 affected403 at risk EG0012 affected184 at risk EG0025 affected94 at risk
Ejection fraction decreased	Investigations	MedDRA (16.0)	Systematic Assessment	EG00011 affected403 at risk EG00112 affected184 at risk EG0020 affected94 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG00066 affected403 at risk EG00125 affected184 at risk EG00215 affected94 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG00030 affected403 at risk EG0014 affected184 at risk EG0026 affected94 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00060 affected403 at risk EG0018 affected184 at risk EG0027 affected94 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00035 affected403 at risk EG00113 affected184 at risk EG0026 affected94 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00022 affected403 at risk EG0017 affected184 at risk EG0020 affected94 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00026 affected403 at risk EG0019 affected184 at risk EG0020 affected94 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00018 affected403 at risk EG00110 affected184 at risk EG0027 affected94 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00047 affected403 at risk EG00114 affected184 at risk EG0026 affected94 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00044 affected403 at risk EG0019 affected184 at risk EG0020 affected94 at risk
Dizziness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG00031 affected403 at risk EG0016 affected184 at risk EG0026 affected94 at risk
Headache	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG000100 affected403 at risk EG00122 affected184 at risk EG00216 affected94 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG00020 affected403 at risk EG00110 affected184 at risk EG0027 affected94 at risk
Paraesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG00028 affected403 at risk EG00111 affected184 at risk EG0029 affected94 at risk
Insomnia	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG00035 affected403 at risk EG0016 affected184 at risk EG0028 affected94 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG00076 affected403 at risk EG00124 affected184 at risk EG00212 affected94 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG00042 affected403 at risk EG00121 affected184 at risk EG0026 affected94 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG00067 affected403 at risk EG0017 affected184 at risk EG00212 affected94 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0009 affected403 at risk EG00120 affected184 at risk EG0020 affected94 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00023 affected403 at risk EG00117 affected184 at risk EG0020 affected94 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG00027 affected403 at risk EG00119 affected184 at risk EG0020 affected94 at risk
Lacrimation increased	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0025 affected94 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0027 affected94 at risk
Pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0025 affected94 at risk
Sinusitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0025 affected94 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected403 at risk EG0010 affected184 at risk EG0025 affected94 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Tucson	Arizona	85704	United States

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D008453	Maytansine
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D000068878	Trastuzumab
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
BG001	Treatment of Physician's Choice	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Trastuzumab Emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	102	403	371	403
EG001	Treatment of Physician's Choice (TPC)	Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.	41	184	148	184
EG002	Trastuzumab Emtansine - Post TPC Treatment Switch	Participants, who switched treatment in the Treatment of Physician's Choice arm to trastuzumab emtansine, were administered trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	19	94	74	94